miR-384-5p regulates inflammation in Candida albicans-induced acute lung injury by downregulating PGC1β and enhancing the activation of Candida albicans-triggered signaling pathways

• Published in: Science progress (1916) 2021-04, Vol.104 (2), p.1-20
• Main Authors: Yu, Dandan, Xu, Chunquan, Tu, Hongxiang, Ye, Aifang, Wu, Lingjian
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Acute Lung Injury - chemically induced; Acute Lung Injury - genetics; Acute Lung Injury - metabolism; AKT protein; Animals; Assaying; Bronchopulmonary infection; Candida albicans; Candida albicans - genetics; Candida albicans - metabolism; Cell activation; Cytokines; Enzyme-linked immunosorbent assay; In vivo methods and tests; Infections; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inhibitors; Lungs; Macrophages; MAP kinase; Mice; MicroRNAs; MicroRNAs - adverse effects; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Mushrooms; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Peroxidase; Polymerase chain reaction; Proto-Oncogene Proteins c-akt - metabolism; Ribonucleic acid; RNA; Signal transduction; Signal Transduction - genetics; Signaling; Stat3 protein; Transfection
• ISSN: 0036-8504; 2047-7163
• DOI: 10.1177/00368504211014361

Acute lung injury (ALI) is one of the most prevalent respiratory syndromes of excessive inflammatory reaction during lung infection. Candida albicans (C. albicans) infection is among the leading causes of ALI. MicroRNAs (miRNAs) regulate the expression of target mRNAs, including those involved in inflammatory processes, by binding to the 3'UTR. To date, the roles of miRNAs in C. albicans-induced ALI remain unclear. In this study, we investigated the role of miR-384-5p in C. albicans-induced ALI and its underlying molecular mechanism. RT-PCR, Western blot, ELISA, Myeloperoxidase (MPO) assay, microRNA target analysis, transient transfection, and luciferase reporter assay were utilized. In vivo study was conducted on mouse model. The expression of miR-384-5p was upregulated and positively correlated with inflammatory cytokine production in lung tissues and RAW264.7 and J774A.1 macrophages infected with C. albicans. The miR-384-5p inhibitor alleviated the inflammatory reaction induced by C. albicans. Target prediction analysis revealed that PGC1β was a target of miR-384-5p, which was further validated by the PGC1β 3'-UTR luciferase assay and the inverse correlation between the expression of miR-384-5p and PGC1β in C. albicans-infected ALI tissues and macrophages. Moreover, macrophages transfected with miR-384-5p mimic exhibited reduced levels of PGC1β. The suppression of the expression of PGC1β by C. albicans infection in the macrophages was abrogated by miR-384-5p inhibitor. Then, we demonstrated that PGC1β played an inhibitory role in C. albicans-induced production of inflammatory cytokines. Furthermore, suppression of miR-384-5p in macrophages inhibited the activation of the NF-κB, MAPK, and Akt signaling pathways triggered by C. albicans, but not the STAT3 pathway. These results demonstrate that miR-384-5p contributes to C. albicans-induced ALI at least in part by targeting PGC1β and enhancing the activation of the NF-κB, MAPK, and Akt inflammatory signaling pathways. Thus, targeting miR-384-5p might exert a protective effect on C. albicans-induced ALI.